Published online before print August 15, 2005, doi: 10.1161/01.HYP.0000174600.51515.e7
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2005;46:1010.)
© 2005 American Heart Association, Inc.
Part 2 Original Articles |
Vascular Sensitivity to Phenylephrine in Rats Submitted to Anaerobic Training and Nandrolone Treatment
From Department of Physiological Sciences (T.S.C., A.P.T., F.K.M.), Faculty of Dentistry of Piracicaba, State University of Campinas, Piracicaba, Sao Paulo, Brazil; Laboratory of Physiology (M.J.C.S.M.), Life Sciences Center, Pontifical Catholic University of Campinas, Campinas, Sao Paulo, Brazil; Laboratory of Biochemistry (C.F.B.), Life Sciences Center, Pontifical Catholic University of Campinas, Campinas, Sao Paulo, Brazil.
Correspondence to Fernanda Klein Marcondes, PhD, Departamento de Ciências Fisiológicas, Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, FOP/UNICAMP, Av. Limeira, 901, 13414-903 Piracicaba, Sao Paulo, Brazil. E-mail fklein{at}fop.unicamp.br
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
The effect of anaerobic physical training and nandrolone treatment on the sensitivity to phenylephrine in thoracic aorta and lipoprotein plasma levels of rats was studied. Sedentary and trained male Wistar rats were treated with vehicle or nandrolone (5 mg/kg IM; twice per week) for 6 weeks. Training was performed by jumping into water (4 sets, 10 repetitions, 30-second rest, 50% to 70% body weight load, 5 days/week, 6 weeks). Two days after the last training session, the animals were killed and blood samples for lipoprotein dosage were obtained. Thoracic aorta was isolated and concentration-effect curves of phenylephrine were performed in intact endothelium and endothelium-denuded aortic rings in the absence or presence of NG-L-arginine-methyl ester. No changes were observed in endothelium-denuded aortic rings. However, in endothelium-intact thoracic aorta, anaerobic physical training induced subsensitivity to phenylephrine (pD2=7.11±0.07) compared with sedentary group (7.55±1.74), and this effect was canceled by the inhibition of nitric oxide synthesis. No difference was observed between trained (7.22±0.07) and sedentary (7.28±0.09) groups treated with nandrolone. Anaerobic training induced an increase in high-density lipoprotein levels in vehicle-treated rats, but there were no changes in nandrolone-treated groups. Training associated with nandrolone induced an increase in low-density lipoprotein levels but no change in the other groups. If altering endothelium-dependent vasodilatation is considered to be a beneficial adaptation to anaerobic physical training, it is concluded that nandrolone treatment worsens animals’ endothelial function, and this effect may be related to lipoprotein blood levels.
Key Words: aorta • endothelium • exercise • lipoproteins • nitric oxide • phenylephrine • rats
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Anabolic androgenic steroids (AAS) are formed from testosterone or one of its derivatives and present both anabolic and androgenic effects. Although the therapeutic indications of AAS are hypogonadism and protein metabolism deficiency, high doses of AAS are frequently used by persons in good health to improve physical performance and appearance, and this practice results in serious health risks.1 With regard to the cardiovascular system, it is well known that AAS can cause stroke,2 ischemic heart disease, myocardial infarction,3 electrocardiographic alterations,4 and sudden cardiac death.5 However, there are few studies about their effects on vascular reactivity. Ferrer et al6 observed an inhibition of endothelium-dependent and endothelium-independent relaxation in the aortic rings of rabbits treated with nandrolone. Vasoconstrictor responses to angiotensin and tyramine, but not to noradrenaline, and vasodepressor responses to acetylcholine are reduced in testosterone-treated dogs.7
Although it is well documented that postexercise hypotension results from a decrease in systemic vascular resistance after aerobic exercise, both in humans and animals,8 there are no data about the vascular effects of anaerobic training. Because the use of supraphysiological doses of AAS is frequently associated with anaerobic exercise, the aim of this study was to determine its influence, as well as that of nandrolone treatment, on the sensitivity to phenylephrine in the thoracic aorta of rats.
Because vascular wall properties are influenced by high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels, and because androgenic steroids have different effects on blood concentration of HDL and LDL,6,9 the serum levels of these lipoproteins were also evaluated.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Animals
Fifty-three male Wistar rats (60 days old) were housed in a temperature-controlled room with a 12:12-hour light-dark cycle. Water and rodent chow were provided ad libitum. After approval by the institutional Committee for Ethics in Animal Research (protocol number 391-1), the rats were randomized into 4 groups: sedentary vehicle-treated, trained vehicle-treated (vehicle=propilenglycol: 0.2 mL body weight twice per week, intramuscularly, for 6 weeks), sedentary nandrolone-treated, and trained nandrolone-treated (nandrolone decanoate; Organon; 5 mg/kg body weight twice per week, intramuscularly, for 6 weeks).10 This dose is comparable to the dose that has been reported as being frequently used by heavy abusers of AAS.11
Training Protocol
The anaerobic training protocol has been described previously.10 Briefly, after 1 week of water adaptation the rats were exercised by jumping into the water (30±2°C), once per day for 5 days, for 5 weeks, carrying a load of 50% body weight strapped to the chest, with 30 seconds of rest between each set of jumps. In the third and fourth training weeks, the animals performed the same exercise carrying a load of 60% body weight, and in the last week, this load was adjusted to 70% of body weight. The weights were attached to the animals’ chests not only to avoid flotation but also to make them exercise against an overload, simulating the squat exercise in water.
Blood Sampling, Tissue Collection, and Analytic Methods
Forty-eight hours after the last exercise session, the rats were anesthetized under halothane, and blood was immediately collected from left renal vein10 and centrifuged to separate the serum. Seric total cholesterol, HDL, and LDL were determined using commercially available kits (Laborlab). The animals were killed by pneumothorax and the thoracic aorta was excised and dissected free of fatty and connective tissue before being cut into 2 3-mm-long to 5-mm-long rings.
Concentration-Effect Curve
Two matched rings, taken from the same animal, were obtained from the middle portion of each aorta and used for functional assays as previously described.12 Briefly, cumulative concentration-effect curves for phenylephrine (PE) were obtained from one ring with intact endothelium and the other without endothelium. To evaluate the role of nitric oxide (NO) on the modulation of thoracic aorta sensitivity to PE, rings with intact endothelium obtained from other animals were incubated for 40 minutes with the NO synthesis inhibitor, NG-L-arginine-methyl-ester (L-NAME) (10–5 M) before concentration-effect curves. Changes in thoracic aorta sensitivity to PE were evaluated by determining the concentration that produced 50% of the maximum response (EC50) and were expressed as the mean negative logarithm (pD2).
Statistical Analysis
Statistical differences were determined by 2-way analysis of variance (ANOVA) followed by the Tukey test. Differences were considered significant at P<0.05. The results are presented as means±SEM.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Neither physical training nor nandrolone treatment altered the maximum response of isolated thoracic aorta to PE (Table). There was subsensitivity to PE in endothelium-intact thoracic aorta rings isolated from trained rats treated with vehicle when compared with the respective sedentary group also treated with vehicle (Table), with 2.8-fold shift to the right in the concentration-effect curve (Figure 1) (P<0.05). However, physical training did not induce any changes in the sensitivity to PE in endothelium-intact thoracic aorta rings isolated from AAS treated animals. There was no difference among the groups in the sensitivity to PE of endothelium-denuded aortic rings (Table and Figure 1) (P>0.05). In the presence of the NO synthesis inhibitor, L-NAME, no alterations in the sensitivity to PE were observed in endothelium-intact thoracic aorta (Figure 2) (P>0.05). No changes were observed in the serum concentration of total cholesterol among the groups (Figure 3) (P>0.05). Rats treated with vehicle and submitted to anaerobic physical training presented higher levels of HDL compared with the respective vehicle sedentary group and trained AAS-treated group (Figure 3) (P<0.05), with no changes between AAS-treated sedentary and trained rats (Figure 3) (P>0.05). Although anaerobic training did not change LDL seric levels in vehicle-treated animals, trained rats treated with nandrolone presented higher levels of LDL compared with the respective sedentary group (Figure 3) (P<0.05).
|
|
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
According to clinical, epidemiological, and pathological studies, aerobic physical activity appears to play an important role in the treatment and prevention of several cardiovascular diseases. Previous studies demonstrated that regular exercise could reduce sympathetic tone,13 depress the pressor response to norepinephrine,14 attenuate baroreflex,15 and improve the bioavailability of endogenous NO in rodents and humans.16,17 Despite some well-documented adaptations with regard to vascular responsiveness after aerobic training, there are no data about the effect of anaerobic training on vascular reactivity.
The anaerobic nature of the high-resistance exercise protocol used in this study was confirmed by a previous study,18 because blood lactate concentration after the second set of jumps was >5.5 mmol/L, the maximal lactate steady-state for rats.19 Moreover, it was demonstrated that this protocol was also efficient for inducing skeletal muscle hypertrophy in rats.19
Because supra-physiological AAS dose users are frequently anaerobic exercise practitioners, it was of interest to evaluate the effects of weight-lifting and AAS treatment on vascular responsiveness. Therefore, the aorta sensitivity to PE was analyzed in rats. Anaerobic training induced subsensitivity to PE in thoracic aorta isolated from vehicle-treated rats compared with the respective sedentary group, with no changes between the 2 groups (trained and sedentary) treated with AAS.
It has been hypothesized that the decrease in arterial pressure, induced by physical exercise, is related to an increase in the vasodilator20–23 and a decrease in the vasoconstrictor responsiveness of blood vessels.24 Support for this hypothesis has been shown in response to different physical exercise programs. Abdominal aorta obtained from treadmill-trained rabbits presented higher endothelium-dependent vasorelaxation induced by acetylcholine (ACh). Thoracic aorta from rats submitted to swimming during 6 weeks showed a decrease in response to PE, but not to potassium chloride,25 as also reported in porcine coronary arteries.26 The aortic subsensitivity to PE observed after anaerobic training in the present study suggests that even in response to the metabolic demands of different physical exercises (aerobic versus anaerobic), vascular adaptations are established to promote a decrease in arterial blood pressure. Moreover, this response can be related to endothelial adaptations to the higher blood flow induced by aerobic and anaerobic exercise training.27
This subsensitivity to PE was only observed in endothelium-intact aortic rings, with no changes in endothelium-denuded aorta, indicating that this effect is endothelium-dependent. Moreover, this effect was canceled by aorta pre-incubation with the nitric oxide synthase (NOS) inhibitor L-NAME.
In the presence of NOS inhibitors, the exercise-induced enhancement of endothelium-dependent vasorelaxation is abolished.20,23 Thoracic aortas isolated from swimming trained rats were also subsensitive to PE, and this effect was caused by an increase in NO production by endothelial cells.25 Delp and Laughin21 reported an upregulation of the expression of endothelial cell NOS mRNA in thoracic aorta from rats submitted to 4 to 10 weeks of training. These results are consistent with others who have reported an increase in NOS mRNA levels in aorta of exercise-trained dogs,28 and in coronary resistance vessels of exercise-trained pigs.29 The expression of inducible NOS and endothelial NOS mRNA were increased in endothelial cells by chronic treadmill training, and chronic exercise blunted PE-induced vascular responses, probably by increasing NO release via inducible NOS, in rat thoracic aorta.30
In this context, the high-intensity training protocol used here may also cause greater release of NO, which diminishes or antagonizes the vasoconstrictor effects of PE. This could explain the subsensitivity observed in thoracic aorta isolated from trained rats compared with the sedentary group. In support of this hypothesis, the lower sensitivity to the vasoconstrictor effect of PE in the trained group was canceled by the inhibition of NO production by L-NAME.
However, when anaerobic training was associated with AAS treatment, no changes in aorta responsiveness to PE were observed, suggesting that this hormone interferes in NO production or in some other mechanisms involved in the vascular effects of PE.
Different results have been reported concerning the effects of AAS in vascular reactivity. Perfused canine hind limb vasoconstrictor responses to angiotensin and tyramine and vasodepressor response to ACh were reduced in testosterone-treated animals, whereas the vasoconstrictor effect of noradrenaline was not altered.7 However, the pressor response elicited by noradrenaline was reduced by testosterone in spinal cats.31
Moreover, the testosterone vascular effect mechanisms have not also been clearly identified. It has been demonstrated that in rat aorta, testosterone causes endothelium-dependent vasorelaxation, which is likely to be mediated by activation of NO activity.32 However, NOS inhibition had no effect on vasorelaxation by testosterone in rabbit aorta.33 Other studies reported that endothelium- and NO-independent vasorelaxation induced by testosterone may involve activation of potassium channels in vascular smooth muscle cells.32,33
There appears to be no studies analyzing the combined effects of anaerobic training and AAS treatment on vascular reactivity. There is one report about the effect of nandrolone decanoate on the vascular reactivity of sedentary male rabbits.6 Nandrolone reduced endothelium-dependent relaxation induced by ACh and endothelium-independent relaxation induced by NO, sodium nitroprusside, and 8-bromo-cGMP in thoracic aortas from these animals. The authors also demonstrated that this effect was mediated by diminished production of ACh and NO vasorelaxation mediator, cGMP. It was concluded that nandrolone decanoate seems to decrease NO-induced vasodilatation by decreasing guanylate cyclase activity in the vascular smooth cells.6
This effect could also explain the data presented here concerning the association of AAS treatment and anaerobic training. In the present study, nandrolone decanoate canceled the subsensitivity to PE observed in thoracic aorta isolated from trained rats and this subsensitivity seems to be related to major NO synthesis induced by chronic exercise. According to Ferrer et al,6 nandrolone decanoate decreased the smooth muscle cell response when anaerobic training was associated with AAS treatment in the present study, and it is suggested that nandrolone seems to block the vasodilatory response to the higher NO synthesis induced by physical training in the thoracic aorta isolated from rats.
However, in contrast to observations by Ferrer et al,6 in the present study nandrolone had no effect on vascular response to PE in sedentary rats. Animal species, AAS treatment duration, and dose administration regimens may explain this difference; in the present study, rats were treated with 5 mg/kg of nandrolone decanoate, twice per week for 6 weeks, whereas in the Ferrer et al6 study, rabbits were treated with one administration of the same AAS, 10 mg/kg once per week for 4, 8, or 12 weeks.
In the present study, it was also observed that anaerobic training induced an increase in HDL seric concentration in rats. Its association with nandrolone treatment canceled this effect and resulted in higher LDL levels compared with the respective AAS sedentary group. According to previous studies, these changes in lipoprotein profile may be related to AAS treatment, and these alterations are able to modify vascular reactivity. It has been reported that the incubation of isolated rabbit aorta with LDL reduced endothelium-dependent relaxation34,35 and guanylate cyclase activation induced by vasodilators.36 This effect is an early marker of atherosclerosis and is antagonized by HDL.36 According to these reports, it may be suggested that the increase in LDL levels observed in trained rats treated with nandrolone in the present study may explain why thoracic aorta isolated from these animals did not present subsensitivity to PE. Higher LDL levels induced by nandrolone could decrease endothelium-dependent relaxation and guanylate cyclase activation, and thus show opposite effects to those induced by training. Moreover, the higher HDL levels observed in trained rats could prevent the effects of LDL in the thoracic aorta.
However, in opposition to some reported effects of AAS on lipoprotein profiles, no changes were observed in sedentary rats treated with nandrolone decanoate. In rabbits, decreased HDL was observed after intramuscular administration of nandrolone decanoate at 4, 8, and 12 weeks, whereas LDL was reduced, unaltered, or increased at 4, 8, and 12 weeks, respectively.6 Differences between rat and rabbit hepatic AAS metabolizing enzymes could account for the diverse effects observed in lipoprotein blood levels in these species.
In humans, the effects of androgenic steroids on lipoprotein levels are not clear. Some studies have shown that AAS causes a reduction37 in the plasmatic concentration of vascular protective HDL38 and an increase in vascular aggressive LDL.37 However, the effects of physiological levels of testosterone were not consistent: testosterone replacement in men is reported to be associated with decreased HDL,39 no change in HDL levels,40 and a favorable effect on HDL levels.41 In addition, the administration of nandrolone decanoate (100 mg/kg, intramuscularly), once per week for 6 weeks did not change HDL or LDL levels of 24 volunteers.9 These discrepancies can be related to the chemical structure of AAS and administration route. Oral administration of 17-alkylated AAS seems to be related to increased HDL and decreased LDL levels, but not to oral or parenteral administration of 17-beta sterified AAS, like nandrolone decanoate,9 for example. Some reports showed that there is a greater induction of HDL catabolic enzyme hepatic triglyceride lipase by oral versus parenteral AAS administration.42,43
In reports on subjects who self-administered AAS, it is difficult to determine the steroid doses that have in fact been used, considering that there is no consistency among such users. Those who consume AAS without any therapeutic indications generally combine at least one oral and several parenteral AAS simultaneously.1,11 Therefore, when evaluating AAS effects on lipoprotein levels, these factors should be taken into account and may explain the disparate results.
In summary, for the first time to our knowledge, it was demonstrated that chronic anaerobic physical training causes a decrease in aorta vascular sensitivity to PE, a beneficial adaptation that seems to be related to the enhancement of NO production and to higher blood concentration of HDL. However, nandrolone treatment blocks this subsensitivity to PE promoted by physical training, probably because this hormone decreases NO vasodilating effect and enhances blood concentration of LDL, damaging the endothelial function of trained animals.
Perspectives
The present study provides evidence that supra-physiological doses of AAS not only induce side effects but also avoid the development of adaptations promoted by physical training. Although the underlying physiological mechanisms of these findings warrant further investigations, it is possible to say that the findings presented here could be helpful in prevention programs for AAS abuse.
|
Acknowledgments |
|---|
This work was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP (02/05427-8) and FAEP/UNICAMP (398/03 and 680/03). T.S.C. was recipient of CAPES scholarship grant and A.P.T. was recipient of FAPESP scholarship grant, Brazil. The authors thank Margery Galbraith for editing the English of the manuscript.
Received April 28, 2005; first decision May 23, 2005; accepted June 8, 2005.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Cunha TS, Cunha NS, Moura MJCS, Marcondes FK. Anabolic androgenic steroids and the relation to the sportive practice. Braz J Pharmac Sci. 2004a; 40: 165–179.
2. Lisiewcz J, Fijalkowski P, Sankowski J. Ischemic cerebral stroke and anabolic steroids (case report). Neurol Neurochir Pol. 1999; 32 (Suppl 6): 137–139.[Medline] [Order article via Infotrieve]
3. Ferenchick GS, Aldeman S. Myocardial infarction associated with anabolic steroid use in a previously healthy 37-year-old weight lifter. Am Heart J. 1992; 241: 507–508.
4. Carnes CA, Dech SJ. Effects of dihydrotestosterone on cardiac inward rectifier K(+) current. Int J Androl. 2002; 25: 210–214.[CrossRef][Medline] [Order article via Infotrieve]
5. Sullivan ML, Martinez CM, Gennis P, Gallagher EJ. The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis. 1998; 41: 1–15.[Medline] [Order article via Infotrieve]
6. Ferrer M, Encabo A, Marín J, Balfagón G. Chronic treatment with the anabolic steroid, nandrolone, inhibits vasodilator responses in rabbit aorta. Eur J Pharmacol. 1994; 252: 233–241.[CrossRef][Medline] [Order article via Infotrieve]
7. Greenberg S, Heitz DC, Long JP. Testosterone-induced depression of adrenergic activity in the perfused canin hindlimb. Proc Soc Exp Biol Med. 1973; 142: 883–888.[CrossRef][Medline] [Order article via Infotrieve]
8. Spier AS, Laughlin MH, Delp MD. Effects of acute and chronic exercise on vasoconstrictor responsiveness of rat abdominal aorta. J Appl Physiol. 1999; 87: 1752–1757.
9. Glazer G, Suchman AL. Lack of demonstrated effect of nandrolone on serum lipids. Metabolism. 1994; 43: 204–210.[CrossRef][Medline] [Order article via Infotrieve]
10. Cunha TS, Tanno AP, Moura MJCS, Marcondes FK. Influence of high-intensity exercise training and anabolic androgenic steroid treatment on rat tissue glycogen content. Life Sci. 2005; 73: 1030–1043.
11. Pope HG Jr, Katz DL. Affective and psychotic symptoms associated with anabolic steroid use. Am J Psychiatry. 1988; 145: 487–490.
12. Moura MJ, Marcondes FK. Influence of estradiol and progesterone on the sensitivity of rat thoracic aorta to noradrenaline. Life Sci. 2001; 68: 881–888.[CrossRef][Medline] [Order article via Infotrieve]
13. Jennings GL, Nelson L, Esler MD, Leonard P, Korner PI. Effects of changes in physical activity on blood pressure and sympathetic tone. J HypertensSuppl. 1984; 2: S139–S141.[Medline] [Order article via Infotrieve]
14. Ames RP, Borkowski AJ, Sicinski AM, Laragh JH. Prolonged infusions of angiotensin II and norepinephrine and blood pressure, electrolyte balance, and aldosterone and cortisol secretion in normal man and in cirrhosis with ascites. J Clin Invest. 1965; 44: 1171–1186.[Medline] [Order article via Infotrieve]
15. DiCarlo SE, Bishop VS. Exercise training attenuates baroreflex regulation of nerve activity in rabbits. Am J Physiol. 1988; 255 (4 Pt 2): H974–H979.[Medline] [Order article via Infotrieve]
16. Kojda G, Cheng YC, Burchfield J, Harrison DG. Dysfunctional regulation of endothelial nitric oxide synthase (eNOS) expression in response to exercise in mice lacking one eNOS gene. Circulation. 2001; 103: 2839–2844.
17. Hambrecht R, Adams V, Erbs S, Linke A, Krankel N, Shu Y, Baither Y, Gielen S, Thiele H, Gummert JF, Mohr FW, Schuler G. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation. 2003; 107: 3152–3158.
18. Cunha TS, Tanno AP, Perez SEA, Robert-Pires CM, Baldissera V, Moura MJCS, Marcondes FK. Characterization of a high-resistance exercise protocol for rats. Annals XIX FeSBE Annual Meeting. 2004b; Águas de Lindóia/SP, Brazil, v. 04.043.
19. Gobatto CA, Sibuya CY, Azevedo JRM, Luciano E, Kokubun E, Mello MAR. Characterization of exercise intensity and of physical training effects using a swimming model for Wistar rats. Motriz. 2001; 7: 57–62.
20. Delp MD, McAllister RM, Laughlin MH. Exercise training alters endothelium-dependent vasoreactivity of rat abdominal aorta. J Appl Physiol. 1993; 75: 1354–1363.
21. Delp MD, Laughlin MH. Time course of enhanced endothelium-mediated dilation in aorta of trained rats. Med Sci Sports Exerc. 1997; 29: 1454–1461.
22. Chen HI, Li HT. Physical conditioning can modulate endothelium-dependent vasorelaxation in rabbits. Arterioscler Thromb. 1993; 13: 852–856.
23. Chen HI, Li HT, Chen CC. Physical conditioning decreases norepinephrine-induced vasoconstriction in rabbits. Possible roles of norepinephrine-evoked endothelium-derived relaxing factor. Circulation. 1994; 90: 970–975.
24. Howard MG, DiCarlo SE, Stallone JN. Acute exercise attenuates phenyleprhine-induced contraction of rabbit isolated aortic rings. Med Sci Sports Exerc. 1992; 24: 1102–1107.
25. Jansakul C. Effect of swimming on vascular reactivity to phenylephrine and KCl in male rats. Br J Pharmacol. 1995; 115: 587–594.[Medline] [Order article via Infotrieve]
26. Oltman CL, Parker JL, Adams HR, Laughlin MH. Effects of exercise training on vasomotor reactivity of porcine coronary arteries. Am J Physiol. 1992; 263: H372–H382.[Medline] [Order article via Infotrieve]
27. Nadaud S, Philippe M, Arnal JF, Michel JB, Soubrier F. Sustained increase in aortic endothelial nitric oxide synthase expression in vivo in a model of chronic high blood flow. Circ Res. 1996; 79: 857–863.
28. Sessa WC, Pritchard K, Seyedi N, Wang J, Hintze TH. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res. 1994; 74: 349–353.
29. Woodman CR, Muller JM, Laughlin MG, Price EM. Inductin of nitric oxide synthase mRNA coronary resistance arteries from exercise-trained pigs. Am J Physiol. 1997; 273: H2572–H2579.
30. Yang AL, Tsai SJ, Jiang MJ, Jen CJ, Chen HI. Chronic exercise increases both inducible and endothelial nitric oxide synthase gene expression in endothelial cells of rat aorta. J Biomed Sci. 2002; 9: 149–155.[CrossRef][Medline] [Order article via Infotrieve]
31. Bhargava KP, Dhawan KN, Saxena RC. Enhancement of noradrenaline pressor responses in testosterone-treated cats. Br J Pharmacol. 1967; 31: 26–31.
32. Honda H, Unemoto T, Kogo H. Different mechanisms for testosterone-induced relaxation of aorta between normotensive and spontaneously hypertensive rats. Hypertension. 1999; 34: 1232–1236.
33. Yue P, Chatterjee K, Beale C, Poole-Wilson PA, Collins P. Testosterone relaxes rabbit coronary arteries and aorta. Circulation. 1995; 91: 1154–1160.
34. Jacobs M, Plane F, Bruckdorfer KR. Native and oxidized low-density lipoproteins have different inhibitory effects on endothelium-derived relaxing factor in the rabbit aorta. Br J Pharmacol. 1990; 100: 21–26.[Medline] [Order article via Infotrieve]
35. Takahashi M, Yui Y, Yasumoto H, Aoyama T, Morishita H, Hattori R, Kawai C. Lipoproteins are inhibitors of endothelium-dependent relaxation of rabbit aorta. Am J Physiol. 1990; 258: H1–H8.[Medline] [Order article via Infotrieve]
36. Schmidt K, Klatt P, Graier WF, Kostner GM, Kukovetz WR. High-density lipoprotein antagonizes the inhibitory effects of oxidized low-density lipoprotein and lysolecithin on soluble guanylyl cyclase. Biochem Biophys Res Commun. 1992; 182: 302–308.[CrossRef][Medline] [Order article via Infotrieve]
37. Webb OL, Laskarzewski PM, Glueck CJ. Severe depression of high-density lipoprotein cholesterol levels in weight lifters and body builders by self-administered exogenous testosterone and anabolic-androgenic steroids. Metabolism. 1984; 33: 971–975.[CrossRef][Medline] [Order article via Infotrieve]
38. Strauss RH, Yesalis CE. Anabolic steroids in the athlete. Annu Rev Med. 1991; 42: 449–457.[CrossRef][Medline] [Order article via Infotrieve]
39. Bagatell CJ, Knopp RH, Vale WW, Rivier JE, Bremner WJ. Physiologic testosterone levels in normal men suppress high-density lipoprotein cholesterol levels. Ann Intern Med. 1992; 116 (12 Pt 1): 967–973.[CrossRef][Medline] [Order article via Infotrieve]
40. Morley JE, Perry HM 3rd, Kaiser FE, Kraenzle D, Jensen J, Houston K, Mattammal M, Perry HM Jr. Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study. J Am Geriatr Soc. 1993; 41: 149–152.[Medline] [Order article via Infotrieve]
41. Hromadova M, Hacik T, Malatinsky E, Riecansky I. Alterations of lipid metabolism in men with hypotestosteronemia. Horm Metab Res. 1991; 23: 392–394.[Medline] [Order article via Infotrieve]
42. Thompson PD, Cullinane EM, Sady SP, Chenevert C, Saritelli AL, Sady MA, Herbert PN. Contrasting effects of testosterone and stanozolol on serum lipoprotein levels. JAMA. 1989; 261: 1165–1168.
43. Friedl KE, Hannan CJ Jr, Jones RE, Plymate SR. High-density lipoprotein cholesterol is not decreased if an aromatizable androgen is administered. Metabolism. 1990; 39: 69–74.[CrossRef][Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  F. L. Rocha, E. C. Carmo, F. R. Roque, N. Y. Hashimoto, L. V. Rossoni, C. Frimm, I. Aneas, C. E. Negrao, J. E. Krieger, and E. M. Oliveira Anabolic steroids induce cardiac renin-angiotensin system and impair the beneficial effects of aerobic training in rats Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3575 - H3583. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||